生物学最新文献

{"title":"RNA export through the nuclear pore complex: pathways, mechanisms, and imaging strategies.","authors":"Donghong Fu, Wenlan Yu, Fanghemei Zhang, Coby Rush, Mark Tingey, Weidong Yang","doi":"10.1080/15476286.2026.2656571","DOIUrl":"10.1080/15476286.2026.2656571","url":null,"abstract":"<p><p>Understanding how RNA molecules traverse the nuclear pore complex (NPC) is central to regulated gene expression because the NPC serves as the selective gateway for RNA export from the nucleus. Distinct RNA classes, including tRNAs, snRNAs, miRNAs, lncRNAs, piRNAs, rRNAs, mRNAs, and circRNAs, follow biogenesis-coupled pathways and engage specific transport receptors and accessory factors to cross this barrier. Recent advances in single-molecule and super-resolution microscopy now enable direct, NPC-resolved visualization of transport for selected RNA species, allowing quantitative measurements of export kinetics, 3D trajectories through the pore, and interaction dynamics with NPC substructures. Here, we review and compare what has been learned from NPC-resolved imaging across RNA classes studied to date, highlighting both shared organizing principles and cargo-specific behaviours. We then describe an experimental and analytical toolbox for NPC-resolved studies of mRNA and pre-ribosomal particle export, including RNA-labelling strategies, major single-molecule and super-resolution modalities, and quantitative metrics used to extract transport parameters. Finally, we discuss key technical and conceptual barriers that currently limit extension to other RNA classes, particularly small and/or low-abundance RNAs, and outline practical strategies to overcome these constraints. Together, this review provides a unified framework for the next generation of single-molecule dissection of RNA dynamics at the nuclear pore.</p>","PeriodicalId":21351,"journal":{"name":"RNA Biology","volume":" ","pages":"1-32"},"PeriodicalIF":4.1,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13078225/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147627042","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Insights into mathematical model with efficient control measures for lumpy skin disease of cattle considering the presence of contaminated environment.","authors":"Faizah J Alanazi, Hegagi M Ali, Essam M Elsaid, Mohamed R Eid, W S Hassanin","doi":"10.1080/17513758.2026.2617692","DOIUrl":"10.1080/17513758.2026.2617692","url":null,"abstract":"<p><p>In this paper, we introduce a mathematical simulation that captures the dynamics of lumpy skin disease (LSD) by considering three key transmission paths: vector-borne, direct cattle-to-cattle contact and environmental contamination. Additionally, this model incorporates three control measures, including vector control, environmental management and isolation/treatment of infected cattle. We perform a comprehensive mathematical analysis to demonstrate the model well-posedness, like proving the existence, uniqueness, positivity and boundedness of the solution. The basic reproduction number (<math><msub><mi>R</mi><mn>0</mn></msub></math>) is calculated. The local and global stability analysis is presented for the disease-free and endemic equilibrium points. Sensitivity analysis for the model parameters is shown, which reveals that isolation and treatment control measures are the most effective in eliminating disease transmission. We construct an objective function to formulate an optimal control problem (OCP) and derive the optimality necessary conditions. Numerical simulations confirm the theoretical findings, demonstrating that strategic implementation of combined control measures can efficiently suppress LSD.</p>","PeriodicalId":48809,"journal":{"name":"Journal of Biological Dynamics","volume":"20 1","pages":"2617692"},"PeriodicalIF":2.7,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146031383","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"数学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The dynamics of hepatitis B virus transmission using a stochastic differential model and feed forward neural network approach.","authors":"Tahir Khan, Muhammad Asif, Muhammad Said, Il Hyo Jung, A S Al-Moisheer, Gul Zaman, Zeeshan Ali","doi":"10.1080/17513758.2026.2629067","DOIUrl":"10.1080/17513758.2026.2629067","url":null,"abstract":"<p><p>Hepatitis B transmission is influenced by environmental variability, immune response and vaccination, making its spread inherently stochastic, while the integration of stochastic modeling with machine learning is particularly important for representing disease uncertainty in varied surroundings. We present a hybrid innovative framework that combines a stochastic epidemiological model with a feed-forward neural network to study hepatitis B virus (HBV) dynamics. We show the well-posedness by establishing the existence of solutions with uniqueness, and analyze extinction and persistence of the disease. In addition, a supervised approach of feed-forward neural network (FFNN) having two hidden layers, each consist of 20 neurons will be used to effectively approximate the dynamics of the model. To evaluate robustness of the network while handling the stochastic model, we evaluate the performance by regression and mean squared error (MSE), and to show a strong alliance among the stochastic trajectories and predicted simulations obtained by the neural network.</p>","PeriodicalId":48809,"journal":{"name":"Journal of Biological Dynamics","volume":"20 1","pages":"2629067"},"PeriodicalIF":2.7,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146167785","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"数学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Redox protection by bacterial glutathione peroxidase drives virulence in <i>Pseudomonas aeruginosa</i>.","authors":"Jadye da Silva Cordeiro, Thiago Macêdo Lopes Correia, Igor Pereira Ribeiro Muniz, Railmara Pereira da Silva, Talita Costa Dos Santos, Leonardo Silva Rocha, Regiane Yatsuda, Julia de Oliveira Borges, Albert Souza Peixoto, Amélia Cristina Mendes de Magalhães, Robson Amaro Augusto da Silva, Flávia Carla Meotti, Raphael Ferreira Queiroz","doi":"10.1080/13510002.2026.2676357","DOIUrl":"10.1080/13510002.2026.2676357","url":null,"abstract":"<p><strong>Background: </strong><i>Pseudomonas aeruginosa</i> relies on antioxidant enzymes to withstand host-derived oxidative stress during infection. Here, we investigated the role of bacterial glutathione peroxidase (GPx) in survival and virulence of the PA14 strain under inflammatory conditions associated with hyperuricemia.</p><p><strong>Methods: </strong>Wild-type (WT) and <i>Δgpx</i> strains were exposed to isolated hypochlorous acid (HOCl), hydrogen peroxide (H₂O₂), tert-butyl hydroperoxide, and urate hydroperoxide (HOOU) or challenged with human neutrophils in the presence or absence of oxidative burst modulators. <i>In vivo</i>, normouricemic and potassium oxonate-induced hyperuricemic mice were intranasally infected with WT or <i>Δgpx</i> strains to assess bacterial burden, inflammation, oxidative damage, and survival.</p><p><strong>Results: </strong>Deletion of <i>gpx</i> increased bacterial susceptibility to all oxidants, particularly HOOU, and significantly reduced survival in activated neutrophils. In mice, <i>Δgpx</i> infection resulted in reduced pulmonary bacterial burden, attenuated neutrophil infiltration, lower oxidative damage, and markedly improved survival compared to WT infection, an effect exacerbated by hyperuricemia in WT-infected animals. These findings demonstrate that GPx detoxifies organic hydroperoxides generated during inflammation, enhancing <i>P. aeruginosa</i> resistance to oxidative killing and promoting virulence.</p><p><strong>Conclusion: </strong>Collectively, our results highlight the importance of redox regulation in bacterial pathogenesis and identify GPx as a potential target for redox-based anti-virulence strategies against multidrug-resistant <i>P. aeruginosa</i>.</p>","PeriodicalId":21096,"journal":{"name":"Redox Report","volume":"31 1","pages":"2676357"},"PeriodicalIF":6.9,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13202656/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147988500","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of prenatal exposure to opioids, cannabis, and polysubstance use with cord blood DNA methylation patterns in a multiancestry cohort.","authors":"Henri Garrison-Desany, Ellen Howerton, Xiumei Hong, Brion Maher, Colleen Pearson, Barry Zuckerman, Guoying Wang, M Daniele Fallin, Terri Beaty, Liming Liang, Xiaobin Wang, Christine Ladd-Acosta","doi":"10.1080/15592294.2026.2670885","DOIUrl":"10.1080/15592294.2026.2670885","url":null,"abstract":"<p><p>Blood DNA methylation patterns are highly predictive of prenatal exposure to smoking, and differential methylation has been associated with maternal alcohol use. We extended this to determine whether DNA methylation patterns in cord blood are associated with prenatal exposure to opioids, cannabis, and polysubstance use. We also evaluated whether DNA methylation patterns have predictive utility. We examined 932 mother-child pairs in the Boston Birth Cohort between 1998 and 2020 with cord blood DNA methylation data. For each substance self-reported within 72 hr after birth, we performed an adjusted linear regression analysis at 865,859 CpG sites to identify related methylation differences. We generated polyepigenetic scores using summary statistics for each exposure and assessed predictive ability using cross-validation and receiver operating characteristic curves. Specificity of methylation associations was evaluated by assessing overlap across exposure summary statistics and using logistic regression for methylation scores, adjusted for concurrent use. We identified methylation changes at 72, 21, and 1 CpG suggestively associated with prenatal exposure to opioids, cannabis, and polysubstance use, respectively (<i>p</i> < 1e-6), in cord blood, reported for the first time for these exposures. We identified two loci associated at epigenome-wide significance with opioids and one with polysubstance use (<i>p</i> < 1e-8). Methylation scores were highly predictive and exposure-specific, with area under the curve accuracy of 91% for opioids, 90% for cannabis, and 93%-98% depending on polysubstance number. These CpGs provide biologic insights for reducing the impact of substance exposure, and these findings may serve as a biomarker of prenatal substance exposure for future studies and potential clinical utility.</p>","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":"21 1","pages":"2670885"},"PeriodicalIF":3.7,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13523970/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148817254","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A relative methylation ordering biomarker of lactylation-related genes predicts prognosis and therapeutic response in cutaneous melanoma.","authors":"Jiayi Ruan, Lingli Wang, Fukang Liu, Yunlong He, Hongdong Li, Guini Hong","doi":"10.1080/15592294.2026.2670909","DOIUrl":"10.1080/15592294.2026.2670909","url":null,"abstract":"<p><p>Cutaneous melanoma (CM) is highly invasive with limited prognostic tools, and the prognostic relevance of lactylation, a novel post-translational modification, remains unexplored. We developed a lactylation-related prognostic model using relative methylation orderings from The Cancer Genome Atlas (TCGA) melanoma cohort (<i>n</i> = 458), which was validated in two dependent cohorts (<i>n</i> = 241). Comprehensive analyses of immune infiltration, therapy efficacy, drug sensitivity, and tumour mutation burden were conducted between high- and low-risk groups. Results showed that 284 lactylation-related genes collected classified TCGA melanoma patients into two clusters with significant survival differences (Kaplan-Meier log-rank test, <i>p</i> = 0.046). Between the two clusters, 279 differentially methylated loci were identified (false discovery rate < 0.05 and |Δβ| >0.1). Based on these loci, 1,743 locus pairs were significantly associated with overall survival (Univariate Cox regression, false discovery rate < 0.05). From these significant pairs, the CM 11 locus-pair prognostic model (CM-LP11) consisting of 11 pairs was constructed, which could effectively stratify patients into high- and low-risk groups with significantly different overall survival across all datasets (all <i>p</i> < 0.05, log-rank test). The high-risk group exhibited an immunosuppressive microenvironment with reduced CD8+ T cells and B cells and increased monocytes (<i>p</i> < 0.05, Wilcoxon test). Functional analysis of methylation differences between risk groups showed significant immune response-related pathways such as antigen processing and presentation. The high- and low-risk patients also exhibited distinct sensitivity to cytotoxic chemotherapy, targeted therapy, and immunotherapy, with the low-risk group showing higher immunophenoscore, cytolytic activity, and tumor mutational burden. CM-LP11 represents a robust lactylation-related prognostic biomarker that predictive survival outcomes and therapeutic responses in CM patients, proving insights for personalized treatment strategies.</p>","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":"21 1","pages":"2670909"},"PeriodicalIF":3.7,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13170386/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147927743","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Macrophage metabolic reprogramming via HIF-1α-glycolysis drives osteoblast ferroptosis and bone loss through an IL-6-STAT3-dependent redox axis.","authors":"Yifan Gu, Kun Wang, Yicong Wang, Ziru Wang, Yiheng Li, Lei Li, Shuai Jiang, Yu Zheng, Run Feng, Min Yang","doi":"10.1080/13510002.2026.2667673","DOIUrl":"10.1080/13510002.2026.2667673","url":null,"abstract":"<p><strong>Background: </strong>Postmenopausal osteoporosis (PMOP) is characterized by exacerbated bone resorption and inadequate bone formation, with macrophage-driven inflammation playing a key role. However, how immunometabolic reprogramming of macrophages modulates osteoblast fate remains unknown.</p><p><strong>Methods: </strong>Using integrated single-cell and bulk transcriptomics, we identified a hypermetabolic macrophage subpopulation in PMOP marrow reliant on HIF-1α-glycolysis. We pharmacologically disrupted this axis with the HDAC inhibitor valproic acid (VPA) and validated its function using the HIF-1α stabilizer DMOG. The paracrine effects on osteoblasts were assessed via conditioned medium, focusing on ferroptosis and differentiation. Therapeutic efficacy was tested in ovariectomized rats.</p><p><strong>Results: </strong>VPA upregulated HIF1AN, enhancing its binding to HIF-1α and promoting its degradation. This suppressed glycolytic flux and M1 polarization, reducing IL-6 secretion. The altered secretome protected osteoblasts from ferroptosis by inhibiting the IL-6/p-STAT3/HIF-1α/TFRC axis and rebalancing GPX4/ACSL4. Osteogenic differentiation was restored. In OVX rats, VPA improved bone mass and microstructure, effects abolished by DMOG.</p><p><strong>Conclusion: </strong>We unveil a macrophage-centric immunometabolic checkpoint that is linked to osteoblast ferroptosis via IL-6/STAT3 signaling. Targeting this HIF-1α-glycolysis axis, exemplified by VPA, represents a novel therapeutic strategy for PMOP.</p>","PeriodicalId":21096,"journal":{"name":"Redox Report","volume":"31 1","pages":"2667673"},"PeriodicalIF":6.9,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13137742/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147819975","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Natural molecule potentiates colistin efficacy <i>in vivo</i> via modulating adaptive LPS modifications and ferroptotic-like damages.","authors":"Hui-Hui Zhang, Yi-Dan Cao, Ying-Ying Xie, Yu-Ze Li, Xiao-Na Fan, Qiu-Yue Diao, Yu-Jiao Liang, Li-Ren He, Zi-Xing Zhong, Li-Juan Xia, Ze-Hua Cui, Xiao-Ping Liao, Xin-Lei Lian, Dong-Hao Zhao, Jian Sun, Hao Ren","doi":"10.1080/21505594.2026.2707759","DOIUrl":"10.1080/21505594.2026.2707759","url":null,"abstract":"<p><p>Colistin holds clinical importance as a last resort therapy against infections caused by multidrug-resistant Gram-negative pathogens. In addition to well-studied plasmid-encoded <i>mcr</i> alleles, the adaptive mechanisms primed by host conditions are increasingly evidenced to be responsible for suboptimal efficacy of colistin in clinical practice, yet have long been neglected. Herein, we reported the identification of baicalein that potentiates colistin killing <i>in vitro</i> and <i>in vivo</i> by manipulating bacterial labile iron pool, where ferrous iron accumulates at the expense of ferric and total iron. This change in iron abundance leads to inactivation of the PmrA/B two-component system and subsequent PmrA/B-dependent lipopolysaccharide modifications, finally promoting colistin to bind and destabilize the bacterial membrane. Meanwhile, increased ferrous iron, in response to colistin-induced ROS, results in ferroptotic-like damage, which generates lethal reactive electrophilic species to deteriorate the essential cellular constituents. These data underscore an exploitable link between iron homeostasis and colistin susceptibility, as both primary and secondary actions of colistin respond to the shifts in cellular labile iron. To sum, this study offers a translationally viable regimen of baicalein-colistin combination against Gram-negative pathogen infection and reveals the cellular labile iron as a generally applicable target for developing next-generation colistin adjuvants.</p>","PeriodicalId":23747,"journal":{"name":"Virulence","volume":" ","pages":"2707759"},"PeriodicalIF":6.8,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13418482/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148550510","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Stability analysis of a multistage compartmental model of infection.","authors":"Jacobs Somnic, Manvel Gasparyan, Shodhan Rao","doi":"10.1080/17513758.2026.2728357","DOIUrl":"https://doi.org/10.1080/17513758.2026.2728357","url":null,"abstract":"<p><p>This paper explores the dynamics of a multistage SIRS model. Using the Lyapunov method as our primary tool, we first revisit the stability analysis of the disease-free and endemic equilibria of a single-stage SIRS model. We then extend the techniques employed in this analysis to enable a similar stability analysis of multistage infection models. In particular, we propose a systematic approach to construct Lyapunov functions for multistage models using symbolic computation in MATLAB. We find that the structure of the constructed Lyapunov functions is closely related to the subsystems or pathways through which the disease progresses. The complete stability analysis for two- and three-stage infection models is presented, and we show that the equilibria are globally asymptotically stable when several parameter constraints are satisfied. Some of these mathematical constraints also provide meaningful epidemiological interpretations.</p>","PeriodicalId":48809,"journal":{"name":"Journal of Biological Dynamics","volume":"20 1","pages":"2728357"},"PeriodicalIF":2.7,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148983904","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"数学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Illuminating ribosome biogenesis disorders through structural biology.","authors":"Sameer Singh, Denis L J Lafontaine","doi":"10.1080/15476286.2026.2701521","DOIUrl":"10.1080/15476286.2026.2701521","url":null,"abstract":"<p><p>Ribosomes are essential nanomachines responsible for synthesizing all cellular proteins. Their production, known as ribosome biogenesis, is a highly complex and energy-intensive process that requires the coordinated action of hundreds of proteins and RNA-based <i>trans</i>-acting factors to assemble and mature the functional ribosomal components. Ribosome biogenesis is increasingly recognized as a key contributor to human disease: excessive ribosome production can fuel tumorigenesis, while insufficient or defective ribosome production is observed in a group of tissue-specific disorders known as ribosomopathies. Although the basis of this tissue specificity remains poorly understood, the most commonly affected systems are the blood, brain, and bones. Recent advances in structural biology have yielded high-resolution snapshots of precursor (pre-)ribosomes at various stages of maturation, offering new insights into how pathogenic variants of ribosomal proteins or assembly factors disrupt critical molecular interactions. In this review, we highlight selected examples where structural information is beginning to illuminate the molecular basis of ribosomopathies.</p>","PeriodicalId":21351,"journal":{"name":"RNA Biology","volume":" ","pages":"1-12"},"PeriodicalIF":4.1,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13371487/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148405828","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}